Platinum Priority – Bladder CancerEditorial by Joseph L. Chin on pp. 524–525 of this issue

Irrigation of Continent Catheterizable Ileal Pouches: Tap Water Can

Replace Sterile Solutions Because It Is Safe, Easy, and Economical

Frederic D. Birkhauser, Pascal Zehnder, Beat Roth, Leander Schurch, Katharina Ochsner,Rita Willener, George N. Thalmann, Fiona C. Burkhard, Urs E. Studer *

Department of Urology, University of Bern, Switzerland

E U R O P E A N U R O L O G Y 5 9 ( 2 0 1 1 ) 5 1 8 – 5 2 3

avai lable at www.sciencedirect .com

journal homepage: www.europeanurology.com

Article info

Article history:Accepted January 3, 2011Published online ahead ofprint on January 12, 2011

Keywords:

Continent urinary reservoir

Urinary tract infection

Irrigation

Isotonic solution

Water

Abstract

Background: Continent catheterizable ileal pouches require regular irrigations to

reduce the risk of bacteriuria and urinary tract infections (UTIs).

Objective: Our aim was to compare the UTI rate, patient friendliness, and costs of

standard sterile irrigation versus irrigation with tap water.

Design, setting, and participants: Twenty-three patients participated in a prospec-

tive randomized two-arm crossover single-center trial. Aseptic intermittent self-

catheterization (ISC) combined with sterile sodium chloride (NaCl) 0.9% irrigation

was compared with clean ISC and irrigation with tap water (H2O) during two study

periods of 90 d each.

Intervention: Patients underwent daily pouch irrigations with NaCl 0.9% solution

or tap water.

Measurements: Urine nitrite dipstick tests were evaluated daily; urine culture

(UC) and patient friendliness were evaluated monthly. Costs were documented.

Results and limitations: A total of 3916 study days with nitrite testing and

irrigation were analyzed, 1876 (48%) in the NaCl arm and 2040 (52%) in the

H2O arm. In the NaCl arm, 418 study days (22%) with nitrite-positive dipsticks

were recorded, 219 d (11%) in the H2O arm, significantly fewer ( p = 0.01). Of the

149 UCs, 96 (64%) were positive, 48 in each arm, revealing a total of 16 different

germs. All patients preferred the H2O method. Monthly costs were up to 20 times

lower in the H2O arm.

Conclusions: Pouch irrigation with sterile NaCl 0.9% solution and tap water had

comparable rates of positive UC. Irrigation with tap water significantly lowered the

incidence of nitrite-positive study days and was substantially less costly and more

patient friendly than NaCl irrigation. We therefore recommend the use of tap water

(or bottled water) instead of sterile NaCl 0.9% solution for daily irrigation of

continent catheterizable ileal pouches.

Trial registration: Australian New Zealand Clinical Trials Registry,

ACTRN12610000618055, http://www.ANZCTR.org.au/ACTRN12610000618055.

aspx.# 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Corresponding author. Department of Urology, University Hospital of Bern, Inselspital, 3010 Bern,Switzerland. Tel. +41 31 632 3641; Fax: +41 31 632 2180.

E-mail address: urs.studer@insel.ch (U.E. Studer).

0302-2838/$ – see back matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2011.01.003

1. Introduction

For patients requiring urinary diversion, a continent

catheterizable urinary reservoir can allow near normal

physical integrity and a good quality of life. The need for

intermittent self-catheterization (ISC), however, leads to an

increased risk of bacteriuria [1]. To reduce the risk of urinary

tract infections (UTIs) and mucus plug formation, daily

pouch irrigation is recommended to eliminate microbes and

evacuate the intestinal mucus [2]. Several studies have

shown that the presence of mucus correlates with bacteri-

uria in patients with bladder substitutes or ileal conduits

[3,4]. Pouch irrigation with a sterile solution (eg, isotonic

saline or Ringer lactate solution) is considered standard.

Table 1 – Patient characteristics

Patients with continent catheterizable ileal

pouch included, n (%)

23 (100)

Median age, yr (range) 61 (29–71)

Sex

- Male, n (%) 3 (13)

- Female, n (%) 20 (87)

Reason for continent catheterizable ileal pouch

- Malignant tumor, n (%) 16 (70)

- Neurogenic bladder dysfunction/pelvic

pain syndrome, n (%)

4 (17)

- Bladder exstrophy, n (%) 2 (9)

- Trauma, n (%) 1 (4)

Median time from construction of pouch

to beginning of study, mo (range)

38 (3–121)

E U R O P E A N U R O L O G Y 5 9 ( 2 0 1 1 ) 5 1 8 – 5 2 3 519

A potential advantage of irrigation with tap water is its

hypo-osmolarity. Levina et al showed that the exposure of

Escherichia coli to a hypo-osmolar medium results in loss of

viability and lysis of the microbes [5]. If tap water would

prove to be as efficient at pouch irrigation as sterile

solutions, it would likely be more patient friendly and less

costly than sterile solutions. The aim of this study was to

test this hypothesis.

2. Materials and methods

A consecutive series of 23 patients (3 men, 20 women; median age: 61

yr; range: 29–71 yr) with a continent catheterizable ileal pouch and no

known preexisting chronic infection was randomized in a prospective

two-arm crossover study. Patients were enrolled in the study a median

of 38 mo (range: 3–121 mo) after pouch construction (Table 1). All

patients gave written informed consent.

The surgical technique employed to construct the ileal pouch is

similar to that used for orthotopic bladder substitution except for the

outlet nipple [6]. An ileal segment of 54 cm resected 25 cm proximal to

the ileocecal valve was used. The ureterointestinal anastomoses were

performed refluxive according to the Nesbit technique into a 15- to 18-

cm-long afferent tubular ileal segment. The nipple preferably was

[()TD$FIG]

Fig. 1 – Study design of the twNaCl = sodium chloride 0.9% solution; H2O = tap wat

formed using the appendix vermiformis. If absent, the ileum was

reconfigured according to the Yang-Monti technique [7] or the fallopian

tube was used instead and fixed to the umbilicus.

The two standardized irrigation techniques studied were aseptic ISC

combined with sterile sodium chloride (NaCl) 0.9% irrigation and clean

ISC combined with tap water (H2O) irrigation. In general, the

concentration of calcium (Ca++) and magnesium (Mg++) ions varies

from 120 to 420 ppm, nitrate concentration from 1 to 28 mg/l, and pH

from 6.9 to 7.7 in Swiss tap water [8].

The crossover from one study arm to the other took place after 90 d.

Because of the need for continuous daily pouch irrigations, there was no

washout period between study arms. Twelve patients started with NaCl

irrigation and 11 with H2O (Fig. 1). Each patient was asked to keep a diary

documenting the results of the nitrite test. Every patient received

written step-by-step procedural descriptions.

In NaCl-arm patients, the umbilicus was cleaned with a solution

containing octenidine dihydrochloride and phenoxyethanol (Octenisept;

Ionto-Comed, Karlsruhe, Germany). Self-catheterization was done using a

sterile ready-to-use disposable hydrophilic-coated catheter (12–14F;

length: 20 cm; SpeediCath [Coloplast, Humlebaek, Denmark] Easy Cath

[Rusch, Teleflex Medical Co, Kenosha, WI, USA). The pouch was irrigated

three times using a sterile 60-ml syringe with sterile NaCl 0.9% solution. In

H2O-arm patients, the umbilicus was cleaned with tap water. Catheters

o-arm crossover study.er; Quest = questionnaire; UC = urine culture.

[()TD$FIG]

Fig. 2 – Percentage of nitrite-positive and nitrite-negative study days asdetermined by daily nitrite testing of urine.

E U R O P E A N U R O L O G Y 5 9 ( 2 0 1 1 ) 5 1 8 – 5 2 3520

and syringes were used up to five times after cleaning with tap water and

drying at room temperature. The remainder of the procedure was the same

as for the NaCl arm except tap water replaced the NaCl 0.9% solution.

At first catheterization in the morning, patients in both arms were

instructed to let the outflowing urine pass directly over a dipstick (Combur

4 Test N; Roche Diagnostics, Basel, Switzerland) to test for nitrite positivity.

In case of nitrite negativity, ISC was repeated at 4-h intervals. In case of

nitrite positivity, the nitrite test and irrigation were repeated at the next

catheterization until nitrite testing became negative. A nitrite-positive

study day was defined as a day with one or more nitrite-positive tests; a

nitrite-negative study day was defined as a day with a negative nitrite test

in the morning. Urine culture (UC) was defined as positive if any number of

bacteria was detected (bacteriuria) and as negative when no bacterial

growth was detected. A symptomatic UTI was defined as a nitrite-positive

dipstick test and positive UC accompanied by symptoms such as fever or

abdominal discomfort. In case of symptomatic UTI, antibiotic treatment

was prescribed. UC were collected at enrolment and at monthly intervals.

Nitrite test results, UC collections, and any antibiotic treatments were

prospectively documented in the patient’s diary.

At the beginning and after completion of each 90-d study arm,

patient friendliness was assessed by a specific questionnaire with six

questions. Due to lack of specificity, validated quality-of-life ques-

tionnaires could not be used. Monthly costs of the material used during

each study period included expenses for catheters and syringes and, in

the NaCl arm, Octenisept and NaCl 0.9% solution.

All statistical analyses were performed by the Institute of Mathe-

matical Statistics and Actuarial Science of the University of Bern,

Switzerland. The nonparametric approach was used for statistical

analysis of the crossover design. Comparison of the nitrite test results

for the two arms was done with the Mann-Whitney test (with exact p

values) applying the nonparametric confidence interval of Hodges and

Lehmann [9]. The paired data of the antibiotic analysis were calculated

with the Wilcoxon sign-rank-test. The patient friendliness question-

naires were evaluated using the Mann-Whitney test (with exact p

values). We assumed that no carryover effect occurred.

3. Results

All 23 patients completed both 90-d study periods except

for 2 patients who refused the crossover to NaCl after the

first study period with H2O.

A total of 3916 (100%) study days were analyzed, 1876 d

(48%) in the NaCl arm and 2040 d (52%) in the H2O arm.

There were 418 (22%) nitrite-positive days in the NaCl arm

Table 2 – Results of urine cultures, antibiotic treatments, and costs

Urine cultures total, n (%)

- Positive urine cultures, any number of bacteria, n (%)

- Positive urine cultures, �10 000 CFU/ml, n (%)

- Positive urine cultures, �100 000 CFU/ml, n (%)

Ratio of positive urine cultures to study days

- Positive urine cultures, any number of bacteria, ratio

- Positive urine cultures, �10 000 CFU/ml, ratio

- Positive urine cultures, �100 000 CFU/ml, ratio

Antibiotic treatment

- Antibiotic treatments required, n

- Median duration of antibiotic treatment, d (range)

Costs per month in CHF/EUR 9

(not included: shipping, waste disposal)

CHF = Swiss franc; EUR = euro; NaCl = sodium chloride 0.9% solution; H2O = tap w

and 219 (11%) in the H2O arm, a significant difference

( p = 0.01; 95% confidence interval, 0.03–0.26) (Fig. 2).

Of the 149 (100%) routinely collected UCs, 96 (64%)

tested positive and 53 (36%) tested negative. Due to the

different number of study days in the two arms, the ratio of

positive UCs to the number of study days was 1 per 39 d in

the NaCl arm and 1 per 43 d in the H2O arm. There were also

no statistically significant differences for positive UC at the

level of both �104 and �105 colony forming units (CFU) per

milliliter between the two arms (Table 2).

In the 12 patients first performing pouch irrigation with

NaCl, the incidence of positive UCs was 29 of 42 (69%) under

NaCl irrigation and 23 of 31 (74%) under H2O irrigation. In

patients starting with H2O irrigations, 23 of 38 positive UCs

(61%) were noted under H2O irrigations and 19 of 32 (59%)

under NaCl. The differences were not significant.

In all positive UCs, 118 strains of bacteria were detected,

59 (50%) in each study arm. The two study arms had similar

microbiologic spectra (Fig. 3). In UCs with �1000 CFU/ml,

most germs were mixed gram-positive or mixed aerobic

flora. Eleven symptomatic UTIs in the NaCl arm compared

NaCl arm H2O arm p value

74 (100) 75 (100) NS

48 (65) 48 (64) NS

33 (45) 33 (44) NS

20 (27) 16 (21) NS

1:39 1:43 NS

1:57 1:62 NS

1:94 1:128 NS

11 4 0.09

7 (5–14) 9 (6–11) NS

40.00/700.00 50.00/37.00

ater; NS = not significant.

[()TD$FIG]

Fig. 3 – Microbiologic spectrum of the 96 positive urine cultures. More than one strain per urine culture is possible.NaCl = sodium chloride 0.9% solution; H2O = tap water.

E U R O P E A N U R O L O G Y 5 9 ( 2 0 1 1 ) 5 1 8 – 5 2 3 521

with four in the H2O arm required antibiotic treatment

( p = 0.09). The two arms had comparable durations of

treatment (Table 2).

All patients preferred the H2O method, adjudging the

NaCl method to be significantly worse in terms of handling,

time required, and impact on professional activity and daily

life (Table 3).

With monthly minimal expenses of Swiss francs (CHF)

940.00 or euro (EUR) 700.00 (30 sterile syringes 60 ml [one

per day], 180 sterile nonhydrophilic single-use catheters

[six per day], NaCl 0.9% solution, aseptic solution), the costs

for the NaCl arm were up to 20 times higher than for the H2O

arm with minimal monthly expenses of CHF 50.00/EUR

37.00 (2 syringes 60 ml, 10 nonhydrophilic single-use

catheters, syringes, and catheters cleaned with tap water

Table 3 – Assessment of patient friendliness

Question

1. How was the handling of this method of reservoir irrigation? 1

to

2. How much time did you need for catheterization and irrigation? M

3. To which extent did this method affect your professional activity? 1

to

4. To which extent did this method have an impact on your daily life? 1

to

5. How would you feel if you would have to catheterize

and irrigate with this method until the end of your life?

1

to

6. Which method did you prefer? [question at the end of the study] ‘‘N

NaCl = sodium chloride 0.9% solution; H2O = tap water.

and reused). In the NaCl arm, costs increased up to CHF

1360.00/EUR 1000.00 if commonly preferred disposable

hydrophilic catheters were used.

4. Discussion

Patients with a continent urinary diversion are at high risk

for UTI [1,10,11] and are therefore advised to irrigate their

pouches regularly for their lifetime. They are usually

instructed to irrigate the pouch with sterile NaCl 0.9%

solution. This prospective study demonstrates that patients

using sterile NaCl 0.9% solution had significantly more

nitrite-positive study days (22%) than the same patients

using tap water (11%). The ratio of positive UCs to number of

study days did not differ significantly between the NaCl arm

Answer options NaCl H2O p value

Median (range) Median (range)

(‘‘very easy’’)

10 (‘‘very difficult’’)

4 (1–10) 1 (1–4) <0.001

inutes 12.5 (5–25) 10 (5–17.5) <0.001

(‘‘not at all’’)

10 (‘‘very much’’)

2 (1–10) 1 (1–8) 0.09

(‘‘not at all’’)

10 (‘‘very much’’)

3.5 (1–9.5) 2 (1–5) <0.001

(‘‘excellent’’)

10 (‘‘miserable’’)

6 (1–10) 2 (1–8) <0.001

aCl’’ or ‘‘H2O’’ 0 23 –

E U R O P E A N U R O L O G Y 5 9 ( 2 0 1 1 ) 5 1 8 – 5 2 3522

(1 of 39) and the H2O arm (1 of 43). Similarly, when only

looking at UC with �104 and �105 CFU/ml, reflecting

significant infections, the ratios were comparable in both

arms and even showed a trend towards a lower incidence of

positive UCs in the H2O arm. In addition, a trend towards

more antibiotic treatments ( p = 0.09) for symptomatic UTI

was noted in the NaCl arm (n = 11) versus the H2O arm

(n = 4).

Symptomatic UTI (n = 15) was much less common than

asymptomatic bacteriuria (n = 96). The 64% incidence of

asymptomatic bacteriuria found in our patients is at the

upper end of what was reported in previous studies on

continent urinary diversions (10–67%) [1,11–13]. The

presence of mainly mixed gram-positive and aerobic flora,

Streptococcus viridans, Staphylococcus, and UC with �1000

CFU/ml strongly suggests contamination of normal cutane-

ous flora [14].

Nitrite levels in the urine depend on the manner of its

production and reduction. The human nitrate-nitrite-nitric

oxide pathway is well known. Nitrate and nitrite are

absorbed in the intestine and excreted by the kidneys [15].

In humans, nitrate-nitrite reduction requires the presence

of bacteria because mammalian cells cannot effectively

metabolize this anion [15,16]. False-negative urine nitrite

tests despite the presence of bacteria may be caused by

reduced nutritional uptake of nitrate or by infection with

bacteria that do not reduce nitrate, such as Staphylococcus

species, Pseudomonas, and some Enterococci [17]. In our

study the significantly higher rate of positive nitrite tests in

the NaCl arm cannot be attributed to differences in human

factors because of the study’s crossover design. It is

probably due to a higher incidence of nitrate-reducing

bacteria in the pouches irrigated with NaCl.

A possible explanation for the lower rates of nitrite-

positive study days and of nitrite-reducing bacteria in the

H2O arm could be the hypo-osmolarity of tap water in

contrast to the iso-osmolarity of the NaCl 0.9% solution.

Microorganisms survive better in an iso-osmolar environ-

ment, whereas an osmotic shift toward a low (or high)

osmolarity environment elicits dramatic changes in bacte-

rial cell structure [18]. Tsapis and Kepes [19] described a

leak of intracellular solutes (neutral and anionic sugars,

endogenous nucleotides, and potassium) in E. coli when

washed with hypo-osmolar solutions. The addition of

various hypo-osmolar solutions caused transient damage

to the cells via osmotic shock; however, no permanent

damage was observed. Bacteria counts were unchanged

when bacteria were diluted in distilled water and then

inoculated onto a culture plate [19]. After an osmotic

downshift, water uptake (phase 1) and release of intracel-

lular solutes (phase 2) were complete within 1–2 min; the

ensuing reaccumulation of solutes (phase 3) was complete

within 10–20 min after the shift [18]. We speculate

therefore that the daily, sometimes repeated irrigation

with tap water may lead to a bacteriostatic state with

impaired cell division and metabolism but not to bacteriol-

ysis. This could explain the significantly lower rate of

nitrite-positive study days in the H2O arm but a similar rate

of positive UCs with a comparable microbiologic spectrum

in both study arms when bacteria are brought back in a

more friendly environment (UC medium). However, such

speculation must be confirmed in further studies. Another

possible reason for the similar rates of bacterial growth in

the UCs of the NaCl and H2O arms and a potential limitation

of the study may be the practice of requiring patients to

collect and ship urine samples themselves. Differences in

urine collection technique and shipping times cannot be

excluded.

From a practical point of view, patients described the

irrigations with NaCl 0.9% solution as more complicated in

handling ( p < 0.001), more time consuming ( p < 0.001),

and having a bigger negative impact on their professional

( p = 0.09) and daily lives ( p < 0.001). The greater logistic

effort of shipping, storing, and disposal of a large and heavy

quantity of material was criticized as not being patient

friendly. All patients preferred irrigations with tap water.

Regarding costs, irrigations with NaCl 0.9% solution (CHF

940.00/EUR 700.00 monthly costs) were far more expensive

than irrigations with tap water (CHF 50.00/EUR 37.00

monthly costs). The determining cost factor for irrigating

with NaCl 0.9% solution was the more frequent use of the

expensive sterile ready-to-use disposable hydrophilic-

coated catheters; the NaCl 0.9% solution itself and the

aseptic cleaning solution and syringes were relatively

cheap. In the H2O arm the same catheter could be used

repeatedly with cleaning. Even if in some countries tap

water would have to be replaced by bottled drinking water,

the costs would still be substantially lower than with

aseptic irrigation with sterile NaCl 0.9% solution.

5. Conclusions

Using tap water for ileal pouch irrigation significantly

reduced the incidence of nitrite-positive study days while

not changing the positive UC rate compared with that of

NaCl 0.9% irrigation with comparable microbiologic spectra.

Similarly, a trend towards fewer antibiotic treatments for

symptomatic UTI was observed in the H2O arm versus the

NaCl arm. All patients preferred the use of tap water as

easier, more patient friendly, and considerably less expen-

sive. We therefore recommend the use of tap water

(or bottled water depending on the local circumstances)

instead of NaCl 0.9% solution for the irrigation of continent

catheterizable ileal pouches.

Author contributions: Urs E. Studer had full access to all the data in the

study and takes responsibility for the integrity of the data and the

accuracy of the data analysis.

Study concept and design: Studer, Birkhauser, Schurch, Burkhard,

Willener, Ochsner, Zehnder, Thalmann.

Acquisition of data: Birkhauser, Ochsner, Zehnder, Roth, Burkhard,

Willener, Thalmann, Studer.

Analysis and interpretation of data: Birkhauser, Studer, Zehnder, Roth.

Drafting of the manuscript: Birkhauser, Zehnder, Studer.

Critical revision of the manuscript for important intellectual content: Studer,

Zehnder.

Statistical analysis: Husler (Institute of Mathematical Statistics and

Actuarial Science of the University of Bern, Switzerland).

E U R O P E A N U R O L O G Y 5 9 ( 2 0 1 1 ) 5 1 8 – 5 2 3 523

Obtaining funding: None.

Administrative, technical, or material support: Ochsner, Willener,

Birkhauser.

Supervision: Studer, Thalmann.

Other (specify): None.

Financial disclosures: I certify that all conflicts of interest, including

specific financial interests and relationships and affiliations relevant

to the subject matter or materials discussed in the manuscript

(eg, employment/affiliation, grants or funding, consultancies, honoraria,

stock ownership or options, expert testimony, royalties, or patents filed,

received, or pending), are the following: None.

Funding/Support and role of the sponsor: None.

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